search
Back to results

Clinical Trial to Assess the Safety and Efficacy of Sodium Stibogluconate (SSG) and AmBisome® Combination, Miltefosine and AmBisome® and Miltefosine Alone for the Treatment Visceral Leishmaniasis in Eastern Africa

Primary Purpose

Primary Visceral Leishmaniasis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Liposomal amphotericin B (AmBisome®) and sodium stibogluconate
Liposomal amphotericin B + miltefosine
Miltefosine
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Visceral Leishmaniasis focused on measuring Phase II, Randomised clinical trial, Visceral Leishmaniasis

Eligibility Criteria

7 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with clinical signs and symptoms of VL and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow or spleen where relevant) on microscopy.
  • Patients aged between 7 (to allow for blood sampling) and 60 years (inclusive) who are able to comply with the protocol.
  • Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age.
  • HIV negative status

Exclusion Criteria:

  • Patients who have received any anti-leishmanial drugs in the last 6 months/ relapse cases.
  • Patients with a negative lymph node/bone marrow (or spleen) smears.
  • Patients with severe protein and or caloric malnutrition (Kwashiorkor or marasmus ; Adults: BMI </= 15, Children W/H<70, presence of oedema)
  • Patients with previous history of hypersensitivity reaction to SSG or Amphotericin B.
  • Patients suffering from a concomitant severe infection such as TB or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication.
  • Patients suffering from other conditions associated with splenomegaly such as schistosomiasis.
  • Patients with previous history of cardiac arrhythmia or an abnormal ECG
  • Patients who are female of child bearing age (all females who have achieved menarche) / pregnant or lactating.
  • Patients with haemoglobin < 5gm/dl.
  • Patients with WBC < 1 x 10³/mm³.
  • Patients with platelets < 40,000/mm³.
  • Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
  • Patients with serum creatinine outside the normal range for age and gender.
  • Major surgical intervention within 2 weeks prior to enrolment.

Sites / Locations

  • Kimalel Health Centre
  • Kassab Hospital
  • El Hassan Centre for Tropical Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Amb+SSG

Amb+Milt

Milt

Arm Description

AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11

AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11

Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28

Outcomes

Primary Outcome Measures

Initial cure: proportion cured at Day 28

Secondary Outcome Measures

Final cure: proportion cured at day 210
Adverse events and serious adverse events occurring in the three study arms

Full Information

First Posted
February 10, 2010
Last Updated
April 21, 2017
Sponsor
Drugs for Neglected Diseases
Collaborators
Gilead Sciences, Paladin Labs Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01067443
Brief Title
Clinical Trial to Assess the Safety and Efficacy of Sodium Stibogluconate (SSG) and AmBisome® Combination, Miltefosine and AmBisome® and Miltefosine Alone for the Treatment Visceral Leishmaniasis in Eastern Africa
Official Title
A Phase II Randomized, Parallel Arm, Open-labeled Clinical Trial to Assess the Safety and Efficacy of the Combination of Sodium Stibogluconate Plus Single Dose AmBisome®, Miltefosine Plus Single Dose AmBisome® and Miltefosine Alone for the Treatment of Primary Visceral Leishmaniasis in Eastern Africa
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
Collaborators
Gilead Sciences, Paladin Labs Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is to assess if shorter combinations of SSG plus single dose AmBisome®, Miltefosine plus single dose AmBisome® and Miltefosine alone are effective in treating visceral leishmaniasis in Eastern Africa.
Detailed Description
The current study intends to look at potential feasible short course combination therapies as well as evaluate (and possibly register) miltefosine in its conventional dose against VL in Sudan and Kenya.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Visceral Leishmaniasis
Keywords
Phase II, Randomised clinical trial, Visceral Leishmaniasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amb+SSG
Arm Type
Experimental
Arm Description
AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11
Arm Title
Amb+Milt
Arm Type
Experimental
Arm Description
AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11
Arm Title
Milt
Arm Type
Experimental
Arm Description
Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28
Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B (AmBisome®) and sodium stibogluconate
Intervention Description
AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11
Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B + miltefosine
Intervention Description
AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11
Intervention Type
Drug
Intervention Name(s)
Miltefosine
Intervention Description
Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28
Primary Outcome Measure Information:
Title
Initial cure: proportion cured at Day 28
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Final cure: proportion cured at day 210
Time Frame
6 months post treatment
Title
Adverse events and serious adverse events occurring in the three study arms
Time Frame
up to day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with clinical signs and symptoms of VL and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow or spleen where relevant) on microscopy. Patients aged between 7 (to allow for blood sampling) and 60 years (inclusive) who are able to comply with the protocol. Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age. HIV negative status Exclusion Criteria: Patients who have received any anti-leishmanial drugs in the last 6 months/ relapse cases. Patients with a negative lymph node/bone marrow (or spleen) smears. Patients with severe protein and or caloric malnutrition (Kwashiorkor or marasmus ; Adults: BMI </= 15, Children W/H<70, presence of oedema) Patients with previous history of hypersensitivity reaction to SSG or Amphotericin B. Patients suffering from a concomitant severe infection such as TB or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication. Patients suffering from other conditions associated with splenomegaly such as schistosomiasis. Patients with previous history of cardiac arrhythmia or an abnormal ECG Patients who are female of child bearing age (all females who have achieved menarche) / pregnant or lactating. Patients with haemoglobin < 5gm/dl. Patients with WBC < 1 x 10³/mm³. Patients with platelets < 40,000/mm³. Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range. Patients with serum creatinine outside the normal range for age and gender. Major surgical intervention within 2 weeks prior to enrolment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monique Wasunna, MD
Organizational Affiliation
Kenya Medical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kimalel Health Centre
City
Kimalel
Country
Kenya
Facility Name
Kassab Hospital
City
Kassab
State/Province
Gedaref
Country
Sudan
Facility Name
El Hassan Centre for Tropical Medicine
City
Doka
State/Province
Gedarif
Country
Sudan

12. IPD Sharing Statement

Citations:
PubMed Identifier
27627654
Citation
Wasunna M, Njenga S, Balasegaram M, Alexander N, Omollo R, Edwards T, Dorlo TP, Musa B, Ali MH, Elamin MY, Kirigi G, Juma R, Kip AE, Schoone GJ, Hailu A, Olobo J, Ellis S, Kimutai R, Wells S, Khalil EA, Strub Wourgaft N, Alves F, Musa A. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial. PLoS Negl Trop Dis. 2016 Sep 14;10(9):e0004880. doi: 10.1371/journal.pntd.0004880. eCollection 2016 Sep.
Results Reference
derived
PubMed Identifier
26573827
Citation
Allison A, Edwards T, Omollo R, Alves F, Magirr D, E Alexander ND. Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups. Trials. 2015 Nov 16;16:522. doi: 10.1186/s13063-015-1018-1.
Results Reference
derived
PubMed Identifier
21718522
Citation
Omollo R, Alexander N, Edwards T, Khalil EA, Younis BM, Abuzaid AA, Wasunna M, Njoroge N, Kinoti D, Kirigi G, Dorlo TP, Ellis S, Balasegaram M, Musa AM. Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Jun 30;12:166. doi: 10.1186/1745-6215-12-166.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://journals.plos.org/plosntds/article/file?type=supplementary&id=info:doi/10.1371/journal.pntd.0004880.s002
Available IPD/Information Comments
Final Study Protocol

Learn more about this trial

Clinical Trial to Assess the Safety and Efficacy of Sodium Stibogluconate (SSG) and AmBisome® Combination, Miltefosine and AmBisome® and Miltefosine Alone for the Treatment Visceral Leishmaniasis in Eastern Africa

We'll reach out to this number within 24 hrs